Field of Invention
The present invention relates generally to sensors for implantation or insertion within a living animal and measurement of a concentration of an analyte in a medium within the living animal. Specifically, the present invention relates to sensors having a membrane over an indicator element on the surface of the sensor body.
Discussion of the Background
A sensor may include an indicator element, such as, for example, indicator molecules embedded or polymerized in or onto a polymer graft (i.e., layer or matrix). For example, in an implantable fluorescence-based glucose sensor, fluorescent indicator molecules may reversibly bind glucose and, when illuminated with excitation light (e.g., light having a wavelength of approximately 378 nm), emit an amount of light (e.g., light in the range of 400 to 500 nm) that depends on whether glucose is bound to the indicator molecule.
If a sensor is implanted in the body of a living animal, the animal's immune system begins to attack the sensor. For instance, if a sensor is implanted in a human, white blood cells attack the sensor as a foreign body, and, in the initial immune system onslaught, neutrophils are the primary white blood cells attacking the sensor. Macrophages and giant cells may further attack the sensor. The defense mechanism of neutrophils and other white blood cells includes the release of highly oxidative substances known as reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), hydroxyl radical (OH⋅), hypochlorite (OCl−), peroxynitrite (OONO−), and superoxide (O2−).
ROS, such as hydrogen peroxide, may degrade indicator molecules. For instance, in indicator molecules having a boronate group, hydrogen peroxide may degrade the indicator molecules by oxidizing the boronate group, thus disabling the ability of the indicator molecule to bind glucose.
In addition, if the sensor is an optical sensor, light (e.g., excitation light, fluorescent light emitted by the indicator molecules) from the sensor may pass through the indicator element or other transparent portions of the sensor. If the sensor has been implanted in animal tissue, the light may be reflected by the tissue or may cause the tissue to fluoresce and return light at a different wavelength. The reflected and fluoresced light from the tissue may return through the indicator element or other transparent part of the sensor and may be received by one or more light detectors (e.g., photodiodes) of the sensor. This results in noise in the signals received by the light detectors.
Moreover, if the animal (e.g., a human patient) is in a brightly lit area, then the light may pass through the patient's skin and be received by the light detectors of the sensor. This could also introduce noise into the signals received by the light detectors. Thus, erroneous sensor readings may occur because light detectors in an implanted sensor may receive additional signals unrelated to the analyte concentration.
There is presently a need in the art for improvements in optical sensor isolation and reducing indicator element degradation.